ObjectiveTo systematically review the clinical efficacy and safety of postpartum hemorrhage (PPH) prophylaxis with a single dose of tranexamic acid (TXA). MethodsThe Embase, PubMed, WanFang Data, VIP, CNKI, ChiCTR and Cochrane Library were electronically retrieved to collect clinical studies related to appraising the efficacy and safety in parturients after cesarean section used TXA perioperatively from inception to September, 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using R software. A trial sequential analysis of outcomes was carried out to investigate the reliability and conclusiveness of findings. ResultsA total of 43 RCTs including 23 497 parturients that compared the prophylactic use of a single dose of TXA with placebo or no treatment in parturients undergoing cesarean delivery. The results of meta-analysis revealed that: 1) there was a significantly reduced risk of PPH (RR=0.52, 95%CI 0.40 to 0.67, P<0.01), total blood loss (SMD=−183.73mL, 95%CI −220.87 to −146.60, P<0.01), need for blood transfusion (RR=0.42, 95%CI 0.30 to 0.60, P<0.01), and use of additional uterotonics (RR=0.55, 95%CI 0.43 to 0.70, P<0.01) with TXA use; 2) there were no statistical differences in thromboembolic events between TXA and control groups (RR=1.05, 95%CI 0.54 to 2.03, P=0.11); and 3) results were consistently in favor of TXA use across subgroups, and trial sequential analyses. ConclusionTaken as a whole, existing evidence suggests that TXA can effectively reduce PPH in patients undergoing cesarean delivery. Further, prophylactic TXA administration for parturients significantly reduced blood loss and need for blood transfusion, without increasing adverse events and use of additional uterotonics, supporting its use as a safe and effective strategy for reducing PPH in this population.